Should You Increase Jardiance to 25 mg?
Yes, increase empagliflozin from 10 mg to 25 mg daily. Although the patient's A1C of 6.9% is near the standard target of <7%, the FDA-approved dose escalation from 10 mg to 25 mg is appropriate for patients tolerating the medication, and this strategy was validated in the pediatric trial where participants not achieving A1C <7% at week 12 were randomized to either remain on 10 mg or increase to 25 mg. 1, 2
Rationale for Dose Escalation
The FDA label explicitly states that "in patients tolerating JARDIANCE, the dose may be increased to 25 mg" once daily, establishing dose escalation as standard practice rather than an exception. 2
The 2025 American Diabetes Association guidelines describe a trial in which youth with type 2 diabetes who did not achieve A1C <7.0% by week 12 underwent a second randomization at week 14 to either remain on 10 mg or increase to 25 mg, demonstrating that dose escalation is the evidence-based approach when glycemic targets are not met. 1
When empagliflozin 10 mg and 25 mg doses were pooled and compared to placebo, the combined group achieved an A1C reduction of 0.84% (P = 0.012), with no episodes of severe hypoglycemia. 1
Expected A1C Reduction with Dose Escalation
The American College of Cardiology reports that empagliflozin reduces A1C by approximately 0.5–0.8% depending on baseline glycemic control and renal function. 3
In a 24-week trial adding empagliflozin to metformin, the 10 mg dose reduced A1C by 0.70% and the 25 mg dose by 0.77% compared to placebo, demonstrating incremental benefit with the higher dose. 4
Increasing from 10 mg to 25 mg can be expected to provide an additional A1C reduction of approximately 0.1–0.3%, which would move this patient's A1C from 6.9% to approximately 6.6–6.8%. 3, 4
Safety Considerations
The risk of hypoglycemia with empagliflozin monotherapy or in combination with metformin is minimal; in the pediatric trial, no severe hypoglycemia occurred during the study period. 1
Adverse events were similar across empagliflozin doses (10 mg vs 25 mg) in clinical trials, with confirmed hypoglycemic events reported in only 1.8% and 1.4% of patients on 10 mg and 25 mg respectively when added to metformin. 4
The most common adverse effects are genital mycotic infections (3.7–4.7%) and urinary tract infections (5.1–5.6%), which do not increase substantially with the higher dose. 4
Cardiovascular and Renal Benefits Independent of Glycemic Control
The American College of Cardiology emphasizes that empagliflozin's cardiovascular and renal benefits are independent of its glucose-lowering effect, and the drug is recommended for patients with established cardiovascular disease regardless of baseline A1C level. 3
Empagliflozin demonstrated a 14% reduction in major adverse cardiac events, a 38% reduction in cardiovascular death, and a 32% reduction in all-cause mortality in the EMPA-REG OUTCOME trial. 5
For cardiovascular risk reduction, the American College of Cardiology states that no dose titration beyond 10 mg is necessary; however, for glycemic control, the 25 mg dose provides superior A1C lowering. 3
Practical Implementation
Increase empagliflozin to 25 mg once daily in the morning, taken with or without food. 2
Reassess A1C in 3 months to confirm achievement of target <7.0%. 3
Monitor for volume depletion, especially if the patient is on diuretics or has reduced oral intake, though this is rarely problematic at standard doses. 2
Important Caveats
Empagliflozin should not be initiated if eGFR is <45 mL/min/1.73 m², and should be discontinued if eGFR persistently falls below this threshold, though it can be continued for cardiovascular and renal protection down to eGFR ≥25 mL/min/1.73 m² in patients with established cardiovascular disease. 2, 3
The glucose-lowering efficacy of empagliflozin decreases substantially with declining renal function: A1C reduction is −0.6% for eGFR 60–90, −0.5% for eGFR 45–60, and only −0.2% for eGFR 30–45 mL/min/1.73 m². 3
If the patient develops dyspnea, nausea, vomiting, or abdominal pain, stop empagliflozin immediately and evaluate for euglycemic diabetic ketoacidosis, a rare but serious complication of SGLT2 inhibitors. 6
Given the patient's intolerance to both metformin and GLP-1 receptor agonists, empagliflozin dose escalation is the most logical next step before considering insulin therapy or other oral agents with less favorable cardiovascular profiles. 3, 7